Drugs Details

Drugs Info of Levemir, Levemir FlexPen
Drugs Details
  • Drugs Type  : Multum
  • Date : 13th Feb 2015 05:18 am
  • Brand Name : Levemir, Levemir FlexPen
  • Generic Name : insulin detemir (Pronunciation: IN su lin DE te mir)
Descriptions

LEVEMIR (insulin detemir [rDNA origin] injection) is a sterile solution of insulin detemir for use as a subcutaneous injection. Insulin detemir is a long-acting (up to 24-hour duration of action) recombinant human insulin analog. LEVEMIR is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification.

Insulin detemir differs from human insulin in that the amino acid threonine in position B30 has been omitted, and a C14 fatty acid chain has been attached to the amino acid B29. Insulin detemir has a molecular formula of C267H402O76N64S6 and a molecular weight of 5916.9. It has the following structure:

Figure 1: Structural Formula of insulin detemir

View Enlarged Table

LEVEMIR is a clear, colorless, aqueous, neutral sterile solution. Each milliliter of LEVEMIR contains 100 units (14.2 mg/mL) insulin detemir, 65.4 meg  inc, 2.06 mg m-cresol, 16.0 mg glycerol, 1.80 mg phenol, 0.89 mg disodium phosphate dihydrate, 1.17 mg sodium chloride, and water for injection. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH. LEVEMIR has a pH of approximately 7.4.

What are the possible side effects of insulin detemir (Levemir, Levemir FlexPen)?

Get emergency medical help if you have any of these signs of insulin allergy: itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating, or feeling like you might pass out.

Call your doctor at once if you have a serious side effect such as:

  • itching, swelling, or redness where you inject insulin detemir;
  • swelling in your hands or feet; or
  • low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Less serious...

Read All Potential Side Effects and See Pictures of Levemir »

What are the precautions when taking insulin detemir (Levemir)?

Before using insulin detemir, tell your doctor or pharmacist if you are allergic to it; or to other types of insulins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Do not use this medication when you have low blood sugar (hypoglycemia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: adrenal/pituitary gland problems, kidney disease, liver disease, thyroid problems.

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can...

Read All Potential Precautions of Levemir »

This monograph has been modified to include the generic and brand name in many instances.

Indications

LEVEMIR is indicated to improve glycemic control in adults and children with diabetes mellitus.

Important Limitations of Use

  • LEVEMIR is not recommended for the treatment of diabetic ketoacidosis. Intravenous rapid-acting or short-acting insulin is the preferred treatment for this condition.

Dosage Administration

Dosing

LEVEMIR is a recombinant human insulin analog for once- or twice-daily subcutaneous administration.

Patients treated with LEVEMIR once-daily should administer the dose with the evening meal or at bedtime.

Patients who require twice-daily dosing can administer the evening dose with the evening meal, at bedtime, or 12 hours after the morning dose.

The dose of LEVEMIR must be individualized based on clinical response. Blood glucose monitoring is essential in all patients receiving insulin therapy.

Patients adjusting the amount or timing of dosing with LEVEMIR should only do so under medical supervision with appropriate glucose monitoring [see WARNINGS AND PRECAUTIONS].

In patients with type 1 diabetes, LEVEMIR must be used in a regimen with rapid-acting or short-acting insulin.

As with all insulins, injection sites should be rotated within the same region (abdomen, thigh, or deltoid) from one injection to the next to reduce the risk of lipodystrophy [see ADVERSE REACTIONS].

LEVEMIR can be injected subcutaneously in the thigh, abdominal wall, or upper arm. As with all insulins, the rate of absorption, and consequently the onset and duration of action, may be affected by exercise and other variables, such as stress, intercurrent illness, or changes in co-administered medications or meal patterns.

When using LEVEMIR with a glucagon-like peptide (GLP)-1 receptor agonist, administer as separate injections. Never mix. It is acceptable to inject LEVEMIR and a GLP-1 receptor agonist in the same body region but the injections should not be adjacent to each other.

Initiation of LEVEMIR Therapy

The recommended starting dose of LEVEMIR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Rapid-acting or short-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements.

The recommended starting dose of LEVEMIR in patients with type 2 diabetes inadequately controlled on oral antidiabetic medications is 10 Units (or 0.1-0.2 Units/kg) given once daily in the evening or divided into a twice daily regimen.

The recommended starting dose of LEVEMIR in patients with type 2 diabetes inadequately controlled on a GLP-1 receptor agonist is 10 Units given once daily in the evening.

LEVEMIR doses should subsequently be adjusted based on blood glucose measurements. The dosages of LEVEMIR should be individualized under the supervision of a healthcare provider.

Converting to LEVEMIR from other insulin therapies

If converting from insulin glargine to LEVEMIR, the change can be done on a unit-to-unit basis.

If converting from NPH insulin, the change can be done on a unit-to-unit basis. However, some patients with type 2 diabetes may require more LEVEMIR than NPH insulin, as observed in one trial [see Clinical Studies].

As with all insulins, close glucose monitoring is recommended during the transition and in the initial weeks thereafter. Doses and timing of concurrent rapid-acting or short-acting insulins or other concomitant antidiabetic treatment may need to be adjusted.

How Supplied

Dosage Forms And Strengths

LEVEMIR solution for injection 100 Unit per mL is available as:

  • 3 mL LEVEMIR FlexPen®
  • 3 mL LEVEMIR FlexTouch®
  • 10 mL vial

Storage And Handling

LEVEMIR is available in the following package sizes: each presentation containing 100 Units of insulin detemir per mL (U-100).

3 mL LEVEMIR FlexPen® NDC 0169-6439-10
3 mL LEVEMIR FlexTouch® NDC 0169-6438-10
10 mL vial NDC 0169-3687-12

FlexPen and FlexTouch can be used with NovoFine® or NovoTwist® disposable needles. Each FlexPen or FlexTouch is for use by a single patient. LEVEMIR FlexPen and LEVEMIR FlexTouch should never be shared between patients, even if the needle is changed.

Storage

Unused (unopened) LEVEMIR should be stored in the refrigerator between 2° and 8°C (36° to 46°F). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. Do not use LEVEMIR if it has been frozen.

Unused (unopened) LEVEMIR can be kept until the expiration date printed on the label if it is stored in a refrigerator. Keep unused LEVEMIR in the carton so that it stays clean and protected from light. If refrigeration is not possible, unused (unopened) LEVEMIR can be kept unrefrigerated at room temperature, below 30°C (86°F) as long as it is kept as cool as possible and away from direct heat and light. Unrefrigerated LEVEMIR should be discarded 42 days after it is first kept out of the refrigerator, even if the FlexPen, FlexTouch or vial still contains insulin.

Vials

After initial use, vials should be stored in a refrigerator, never in a freezer. If refrigeration is not possible, the in-use vial can be kept unrefrigerated at room temperature, below 30°C (86°F) as long as it is kept as cool as possible and away from direct heat and light. Refrigerated LEVEMIR vials should be discarded 42 days after initial use. Unrefrigerated LEVEMIR vials should be discarded 42 days after they are first kept out of the refrigerator.

LEVEMIR FlexPen or LEVEMIR FlexTouch:

After initial use, the LEVEMIR FlexPen or LEVEMIR FlexTouch must NOT be stored in a refrigerator and must NOT be stored with the needle in place. Keep the opened (in use) LEVEMIR FlexPen or LEVEMIR FlexTouch away from direct heat and light at room temperature, below 30°C (86°F). Unrefrigerated LEVEMIR FlexPen or LEVEMIR FlexTouch should be discarded 42 days after they are first kept out of the refrigerator.

The storage conditions are summarized in Table 13:

Table 13: Storage Conditions for LEVEMIR FlexPen, LEVEMIR FlexTouch, and vial

  Not in-use (unopened) Refrigerated Not in-use (unopened) Room Temperature (below 30°C) In-use (opened)
3 mL LEVEMIR FlexPen Until expiration date 42 days* 42 days* Room Temperature (below 30°C) (Do not refrigerate)
3 mL LEVEMIR FlexTouch Until expiration date 42 days* 42 days* Room Temperature (below 30°C) (Do not refrigerate)
10 mL vial Until expiration date 42 days* 42 days* Refrigerated or Room Temperature (below 30°C)
*The total time allowed at room temperature (below 30°C) is 42 days regardless of whether the product is in-use or not in-use.

Preparation and handling

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. LEVEMIR should be inspected visually prior to administration and should only be used if the solution appears clear and colorless.

Mixing and diluting: LEVEMIR must NOT be mixed or diluted with any other insulin or solution [See WARNINGS AND PRECAUTIONS].

Manufactured By: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark. Revised: 10/2013

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

The following adverse reactions are discussed elsewhere:

  • Hypoglycemia [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity and allergic reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The frequencies of adverse reactions (excluding hypoglycemia) reported during LEVEMIR clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Tables 1-4 below. See Tables 5 and 6 for the hypoglycemia findings.

In the LEVEMIR add-on to liraglutide+metformin trial, all patients received liraglutide 1.8 mg + metformin during a 12-week run-in period. During the run-in period, 167 patients (17% of enrolled total) withdrew from the trial: 76 (46% of withdrawals) of these patients doing so because of gastrointestinal adverse reactions and 15 (9% of withdrawals) doing so due to other adverse events. Only those patients who completed the run-in period with inadequate glycemic control were randomized to 26 weeks of add-on therapy with LEVEMIR or continued, unchanged treatment with liraglutide 1.8 mg + metformin. During this randomized 26-week period, diarrhea was the only adverse reaction reported in ≥ 5% of patients treated with liraglutide 1.8 mg + metformin (11.7%) and greater than in patients treated with liraglutide 1.8 mg and metformin alone (6.9%).

In two pooled trials, a total of 1155 adults with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=767) or NPH (n=388). The mean duration of exposure to LEVEMIR was 153 days, and the total exposure to LEVEMIR was 321 patient-years. The most common adverse reactions are summarized in Table 1.

Table 1: Adverse reactions (excluding hypoglycemia) in two pooled clinical trials of 16 weeks and 24 weeks duration in adults with type 1 diabetes (adverse reactions with incidence ≥ 5%)

  LEVEMIR, %
(n = 767)
NPH, %
(n = 388)
Upper respiratory tract infection 26.1 21.4
Headache 22.6 22.7
Pharyngitis 9.5 8.0
Influenza-like illness 7.8 7.0
Abdominal Pain 6.0 2.6

A total of 320 adults with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=161) or insulin glargine (n=159). The mean duration of exposure to LEVEMIR was 176 days, and the total exposure to LEVEMIR was 78 patient-years. The most common adverse reactions are summarized in Table 2.

Table 2: Adverse reactions (excluding hypoglycemia) in a 26-week trial comparing insulin aspart + LEVEMIR to insulin aspart + insulin glargine in adults with type 1 diabetes (adverse reactions with incidence ≥ 5%)

  LEVEMIR, %
(n =161)
Glargine, %
(n =159)
Upper respiratory tract infection 26.7 32.1
Headache 14.3 19.5
Back pain 8.1 6.3
Influenza-like illness 6.2 8.2
Gastroenteritis 5.6 4.4
Bronchitis 5.0 1.9

In two pooled trials, a total of 869 adults with type 2 diabetes were exposed to individualized doses of Levemir (n=432) or NPH (n=437). The mean duration of exposure to LEVEMIR was 157 days, and the total exposure to LEVEMIR was 186 patient-years. The most common adverse reactions are summarized in Table 3.

Table 3: Adverse reactions (excluding hypoglycemia) in two pooled clinical trials of 22 weeks and 24 weeks duration in adults with type 2 diabetes (adverse reactions with incidence ≥ 5%)

  LEVEMIR, %
(n = 432)
NPH, %
(n = 437)
Upper respiratory tract infection 12.5 11.2
Headache 6.5 5.3

A total of 347 children and adolescents (6-17 years) with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=232) or NPH (n=115). The mean duration of exposure to LEVEMIR was 180 days, and the total exposure to LEVEMIR was 114 patient-years. The most common adverse reactions are summarized in Table 4.

Table 4: Adverse reactions (excluding hypoglycemia) in one 26-week clinical trial of children and adolescents with type 1 diabetes (adverse reactions with incidence ≥ 5%)

  LEVEMIR, %
(n = 232)
NPH, %
(n =115)
Upper respiratory tract infection 35.8 42.6
Headache 31.0 32.2
Pharyngitis 17.2 20.9
Gastroenteritis 16.8 11.3
Influenza-like illness 13.8 20.9
Abdominal pain 13.4 13.0
Pyrexia 10.3 6.1
Cough 8.2 4.3
Viral infection 7.3 7.8
Nausea 6.5 7.0
Rhinitis 6.5 3.5
Vomiting 6.5 10.4

Pregnancy

A randomized, open-label, controlled clinical trial has been conducted in pregnant women with type 1 diabetes. [see Use in Specific Populations]

Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including LEVEMIR [see WARNINGS AND PRECAUTIONS].

Tables 5 and 6 summarize the incidence of severe and non-severe hypoglycemia in the LEVEMIR clinical trials.

For the adult trials and one of the pediatric trials (Study D), severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring assistance of another person and associated with either a plasma glucose value below 56 mg/dL (blood glucose below 50 mg/dL) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. For the other pediatric trial (Study I), severe hypoglycemia was defined as an event with semi-consciousness, unconsciousness, coma and/or convulsions in a patient who could not assist in the treatment and who may have required glucagon or intravenous glucose.

For the adult trials and pediatric Study D, non-severe hypoglycemia was defined as an asymptomatic or symptomatic plasma glucose < 56 mg/dL (or equivalently blood glucose < 50 mg/dL as used in Study A and C) that was self-treated by the patient. For pediatric Study I, non-severe hypoglycemia included asymptomatic events with plasma glucose < 65 mg/dL as well as symptomatic events that the patient could self-treat or treat by taking oral therapy provided by the caregiver.

The rates of hypoglycemia in the LEVEMIR clinical trials (see Clinical Studies for a description of the study designs) were comparable between LEVEMIR-treated patients and non-LEVEMIR-treated patients (see Tables 5 and 6).

Table 5: Hypoglycemia in Patients with Type 1 Diabetes

View Enlarged Table

Table 6: Hypoglycemia in Patients with Type 2 Diabetes

View Enlarged Table
Insulin Initiation and Intensification of Glucose Control

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Lipodystrophy

Long-term use of insulin, including LEVEMIR, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy [see DOSAGE AND ADMINISTRATION].

Weight Gain

Weight gain can occur with insulin therapy, including LEVEMIR, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria [see Clinical Studies].

Peripheral Edema

Insulin, including LEVEMIR, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Allergic Reactions

Local Allergy

As with any insulin therapy, patients taking LEVEMIR may experience injection site reactions, including localized erythema, pain, pruritus, urticaria, edema, and inflammation. In clinical studies in adults, three patients treated with LEVEMIR reported injection site pain (0.25%) compared to one patient treated with NPH insulin (0.12%). The reports of pain at the injection site did not result in discontinuation of therapy.

Rotation of the injection site within a given area from one injection to the next may help to reduce or prevent these reactions. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique. Most minor reactions to insulin usually resolve in a few days to a few weeks.

Systemic Allergy

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including LEVEMIR, and may be life-threatening [see WARNINGS AND PRECAUTIONS].

Antibody Production

All insulin products can elicit the formation of insulin antibodies. These insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In phase 3 clinical trials of LEVEMIR, antibody development has been observed with no apparent impact on glycemic control.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of LEVEMIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported during post-approval use of LEVEMIR in which other insulins, particularly rapid-acting or short-acting insulins, have been accidentally administered instead of LEVEMIR [see PATIENT INFORMATION]. To avoid medication errors between LEVEMIR and other insulins, patients should be instructed always to verify the insulin label before each injection.

Read the Levemir (insulin detemir) Side Effects Center for a complete guide to possible side effects

Learn More »

Interactions

A number of medications affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.

The following are examples of medications that may increase the blood-glucose-lowering effect of insulins including LEVEMIR and, therefore, increase the susceptibility to hypoglycemia: oral antidiabetic medications, pramlintide acetate, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.

The following are examples of medications that may reduce the blood-glucose-lowering effect of insulins including LEVEMIR: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).

Beta-blockers, clonidine, lithium salts, and alcohol may either increase or decrease the blood-glucoselowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

Read the Levemir Drug Interactions Center for a complete guide to possible interactions

Learn More »

This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Dosage Adjustment And Monitoring

Glucose monitoring is essential for all patients receiving insulin therapy. Changes to an insulin regimen should be made cautiously and only under medical supervision.

Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in the insulin dose or an adjustment of concomitant anti-diabetic treatment.

As with all insulin preparations, the time course of action for LEVEMIR may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the local blood supply, local temperature, and physical activity.

Administration

LEVEMIR should only be administered subcutaneously.

Do not administer LEVEMIR intravenously or intramuscularly. The intended duration of activity of LEVEMIR is dependent on injection into subcutaneous tissue. Intravenous or intramuscular administration of the usual subcutaneous dose could result in severe hypoglycemia.

Do not use LEVEMIR in insulin infusion pumps.

Do not dilute or mix LEVEMIR with any other insulin or solution. If LEVEMIR is diluted or mixed, the pharmacokinetic or pharmacodynamic profile (e.g., onset of action, time to peak effect) of LEVEMIR and the mixed insulin may be altered in an unpredictable manner.

Hypoglycemia

Hypoglycemia is the most common adverse reaction of insulin therapy, including LEVEMIR. The risk of hypoglycemia increases with intensive glycemic control.

When a GLP-1 receptor agonist is used in combination with LEVEMIR, the LEVEMIR dose may need to be lowered or more conservatively titrated to minimize the risk of hypoglycemia [see ADVERSE REACTIONS].

All patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person or parenteral glucose infusion, or glucagon administration has been observed in clinical trials with insulin, including trials with LEVEMIR.

The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), exercise, and concomitant medications may also alter the risk of hypoglycemia [see DRUG INTERACTIONS].

The prolonged effect of subcutaneous LEVEMIR may delay recovery from hypoglycemia.

As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control [see DRUG INTERACTIONS]. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia.

Hypersensitivity And Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LEVEMIR.

Renal Impairment

No difference was observed in the pharmacokinetics of insulin detemir between non-diabetic individuals with renal impairment and healthy volunteers. However, some studies with human insulin have shown increased circulating insulin concentrations in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with renal impairment [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

Non-diabetic individuals with severe hepatic impairment had lower systemic exposures to insulin detemir compared to healthy volunteers. However, some studies with human insulin have shown increased circulating insulin concentrations in patients with liver impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with hepatic impairment [see CLINICAL PHARMACOLOGY].

Drug interactions

Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia [see DRUG INTERACTIONS].

Fluid Retention And Heart Failure With Concomitant Use of PPAR-Gamma Agonists

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including LEVEMIR, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Patient Counseling Information

See FDA-Approved Patient Labeling (Patient Information and Instructions for Use)

Instructions for Patients

Patients should be informed that changes to insulin regimens must be made cautiously and only under medical supervision. Patients should be informed about the potential side effects of insulin therapy, including hypoglycemia, weight gain, lipodystrophy (and the need to rotate injection sites within the same body region), and allergic reactions. Patients should be informed that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery.

Accidental mix-ups between LEVEMIR and other insulins, particularly short-acting insulins, have been reported. To avoid medication errors between LEVEMIR and other insulins, patients should be instructed to always check the insulin label before each injection.

LEVEMIR must only be used if the solution is clear and colorless with no particles visible. Patients must be advised that LEVEMIR must NOT be diluted or mixed with any other insulin or solution.

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients should be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.

Patients should receive proper training on how to use Levemir. Instruct patients that when injecting Levemir, they must press and hold down the dose button until the dose counter shows 0 and then keep the needle in the skin and count slowly to 6. When the dose counter returns to 0, the prescribed dose is not completely delivered until 6 seconds later. If the needle is removed earlier, they may see a stream of insulin coming from the needle tip. If so, the full dose will not be delivered (a possible under-dose may occur by as much as 20%), and they should increase the frequency of checking their blood glucose levels and possible additional insulin administration may be necessary.

  • If 0 does not appear in the dose counter after continuously pressing the dose button, the patient may have used a blocked needle. In this case they would not have received any insulin – even though the dose counter has moved from the original dose that was set.
  • If the patient did have a blocked needle, instruct them to change the needle as described in Section 5 of the Instructions for Use and repeat all steps in the IFU starting with Section 1: Prepare your pen with a new needle. Make sure the patient selects the full dose needed.

Patients with diabetes should be advised to inform their healthcare professional if they are pregnant or are contemplating pregnancy. Refer patients to the LEVEMIR “Patient Information” for additional information.

Never Share a LEVEMIR FlexPen or LEVEMIR FlexTouch Between Patients

Counsel patients that they should never share a LEVEMIR FlexPen or LEVEMIR FlexTouch with another person, even if the needle is changed. Sharing of the FlexPen or FlexTouch between patients may pose a risk of transmission of infection.

Nonclinical Toxicology

Carcinogenicity, Mutagenicity, Impairment of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed. Insulin detemir tested negative for genotoxic potential in the in vitro reverse mutation study in bacteria, human peripheral blood lymphocyte chromosome aberration test, and the in vivo mouse micronucleus test. In a fertility and embryonic development study, insulin detemir was administered to female rats before mating, during mating, and throughout pregnancy at doses up to 300 nmol/kg/day (3 times a human dose of 0.5 Units/kg/day, based on plasma AUC ratio). There were no effects on fertility in the rat.

Use In Specific Populations

Pregnancy

Pregnancy Category B
Risk Summary

The background risk of birth defects, pregnancy loss, or other adverse events that exists for all pregnancies is increased in pregnancies complicated by hyperglycemia. Female patients should be advised to tell their physician if they intend to become, or if they become pregnant while taking LEVEMIR. A randomized controlled clinical trial of pregnant women with type I diabetes using LEVEMIR during pregnancy did not show an increase in the risk of fetal abnormalities. Reproductive toxicology studies in non-diabetic rats and rabbits that included concurrent human insulin control groups indicated that insulin detemir and human insulin had similar effects regarding embryotoxicity and teratogenicity that were attributed to maternal hypoglycemia.

Clinical Considerations

The increased risk of adverse events in pregnancies complicated by hyperglycemia may be decreased with good glucose control before conception and throughout pregnancy. Because insulin requirements vary throughout pregnancy and in the post-partum period, careful monitoring of glucose control is essential in pregnant women.

Human Data

In an, open-label, clinical study, women with type 1 diabetes who were (between weeks 8 and 12 of gestation) or intended to become pregnant were randomized 1:1 to LEVEMIR (once or twice daily) or NPH insulin (once, twice or thrice daily). Insulin aspart was administered before each meal. A total of 152 women in the LEVEMIR arm and 158 women in the NPH arm were or became pregnant during the study (Total pregnant women = 310). Approximately one half of the study participants in each arm were randomized as pregnant and were exposed to NPH or to other insulins prior to conception and in the first 8 weeks of gestation. In the 310 pregnant women, the mean glycosylated hemoglobin (HbA1c) was < 7% at 10, 12, and 24 weeks of gestation in both arms. In the intent-to-treat population, the adjusted mean HbA1c (standard error) at gestational week 36 was 6.27% (0.053) in LEVEMIR-treated patient (n=138) and 6.33% (0.052) in NPH-treated patients (n=145); the difference was not clinically significant.

Adverse reactions in pregnant patients occurring at an incidence of ≥ 5% are shown in Table 7. The two most common adverse reactions were nasopharyngitis and headache. These are consistent with findings from other type 1 diabetes trials (see Table 1), and are not repeated in Table 7.

The incidence of adverse reactions of pre-eclampsia was 10.5% (16 cases) and 7.0% (11 cases) in the LEVEMIR and NPH insulin groups respectively. Out of the total number of cases of pre-eclampsia, eight (8) cases in the LEVEMIR group and 1 case in the NPH insulin group required hospitalization. The rates of pre-eclampsia observed in the study are within expected rates for pregnancy complicated by diabetes. Pre-eclampsia is a syndrome defined by symptoms, hypertension and proteinuria; the definition of pre-eclampsia was not standardized in the trial making it difficult to establish a link between a given treatment and an increased risk of pre-eclampsia. All events were considered unlikely related to trial treatment. In all nine (9) cases requiring hospitalization the women had healthy infants. Events of hypertension, proteinuria and edema were reported less frequently in the LEVEMIR group than in the NPH insulin group as a whole. There was no difference between the treatment groups in mean blood pressure during pregnancy and there was no indication of a general increase in blood pressure.

In the NPH insulin group there were 6 serious adverse reactions in four mothers of the following placental disorders, 'Placenta previa', 'Placenta previa hemorrhage', and 'Premature separation of placenta' and 1 serious adverse reaction of 'Antepartum haemorrhage'. There were none reported in the LEVEMIR group.

The incidence of early fetal death (abortions) was similar in LEVEMIR and NPH treated patients; 6.6% and 5.1%, respectively. The abortions were reported under the following terms: 'Abortion spontaneous', 'Abortion missed', 'Blighted ovum', 'Cervical incompetence' and 'Abortion incomplete'.

Table 7: Adverse reactions during pregnancy in a trial comparing insulin aspart + LEVEMIR to insulin aspart + NPH insulin in pregnant women with type 1 diabetes (adverse reactions with incidence ≥ 5%)

  LEVEMIR, %
(n =152)
NPH, %
(n =158)
Anemia 13.2 10.8
Diarrhea 11.8 5.1
Pre-eclampsia 10.5 7.0
Urinary tract infection 9.9 5.7
Gastroenteritis 8.6 5.1
Abdominal pain upper 5.9 3.8
Vomiting 5.3 4.4
Abortion spontaneous 5.3 2.5
Abdominal pain 5.3 6.3
Oropharyngeal pain 5.3 6.3
*Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The proportion of subjects experiencing severe hypoglycemia was 16.4% and 20.9% in LEVEMIR and NPH treated patients respectively. The rate of severe hypoglycemia was 1.1 and 1.2 events per patientyear in LEVEMIR and NPH treated patients respectively. Proportion and incidence rates for non-severe episodes of hypoglycemia were similar in both treatment groups (Table 8).

Table 8: Hypoglycemia in Pregnant Women with Type 1 Diabetes

    Study G Type 1 Diabetes Pregnancy In combination with insulin aspart
LEVEMIR NPH
Severe hypoglycemia* Percent of patients with at least 1 event (n/total N) 16.4 (25/152) 20.9 (33/158)
Events/patient/year 1.1 1.2
Non-severe hypoglycemia* Percent of patients with at least 1 event (n/total N) 94.7 (144/152) 92.4 (146/158)
Events/patient/year 114.2 108.4
* For definition regarding severe and non-severe hypoglycemia see ADVERSE REACTIONS, Hypoglycemia. In about a quarter of infants, LEVEMIR was detected in the infant cord blood at levels above the lower level of quantification ( < 25 pmol/L).

No differences in pregnancy outcomes or the health of the fetus and newborn were seen with LEVEMIR use.

Animal Data

In a fertility and embryonic development study, insulin detemir was administered to female rats before mating, during mating, and throughout pregnancy at doses up to 300 nmol/kg/day (3 times a human dose of 0.5 Units/kg/day, based on plasma area under the curve (AUC) ratio). Doses of 150 and 300 nmol/kg/day produced numbers of litters with visceral anomalies. Doses up to 900 nmol/kg/day (approximately 135 times a human dose of 0.5 Units/kg/day based on AUC ratio) were given to rabbits during organogenesis. Drug and dose related increases in the incidence of fetuses with gallbladder abnormalities such as small, bilobed, bifurcated, and missing gallbladders were observed at a dose of 900 nmol/kg/day. The rat and rabbit embryofetal development studies that included concurrent human insulin control groups indicated that insulin detemir and human insulin had similar effects regarding embryotoxicity and teratogenicity suggesting that the effects seen were the result of hypoglycemia resulting from insulin exposure in normal animals.

Nursing Mothers

It is unknown whether LEVEMIR is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, use caution when administering LEVEMIR to a nursing woman. Women with diabetes who are lactating may require adjustments of their insulin doses.

Pediatric Use

The pharmacokinetics, safety and effectiveness of subcutaneous injections of LEVEMIR have been established in pediatric patients (age 2 to 17 years) with type 1 diabetes [see CLINICAL PHARMACOLOGY and Clinical Studies]. LEVEMIR has not been studied in pediatric patients younger than 2 years of age with type 1 diabetes. LEVEMIR has not been studied in pediatric patients with type 2 diabetes.

The dose recommendation when converting to LEVEMIR is the same as that described for adults [see DOSAGE AND ADMINISTRATION and Clinical Studies]. As in adults, the dosage of LEVEMIR must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.

Geriatric Use

In controlled clinical trials comparing LEVEMIR to NPH insulin or insulin glargine, 64 of 1624 patients (3.9%) in the type 1 diabetes trials and 309 of 1082 patients (28.6%) in the type 2 diabetes trials were ≥ 65 years of age. A total of 52 (7 type 1 and 45 type 2) patients (1.9%) were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes, particularly for patients ≥ 65 years of age in the type 1 diabetes trials and for patients ≥ 75 years of age in all trials limits conclusions. Greater sensitivity of some older individuals cannot be ruled out. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the elderly.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia [see WARNINGS AND PRECAUTIONS].

ContrainDications

LEVEMIR is contraindicated in patients with hypersensitivity to LEVEMIR or any of its excipients. Reactions have included anaphylaxis [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

The primary activity of insulin detemir is the regulation of glucose metabolism. Insulins, including insulin detemir“, exert their” specific action through binding to insulin receptors. Receptor-bound insulin lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and adipose tissue and by inhibiting the output of glucose from the liver. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis, and enhances protein synthesis.

Pharmacodynamics

Insulin detemir“ is a soluble, long-acting basal human insulin analog with up to a 24-hour duration of action. The pharmacodynamic profile of LEVEMIR is relatively constant with no pronounced peak.

The duration of action of LEVEMIR is mediated by slowed systemic absorption of insulin detemir molecules from the injection site due to self-association of the drug molecules. In addition, the distribution of insulin detemir to peripheral target tissues is slowed because of binding to albumin.

Figure 2 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 homs after the subcutaneous injection of LEVEMIR or NPH insulin. The mean time between injection and the end of pharmacological effect for insulin detemir” ranged from 7.6 hours to > 24 homs (24 homs was the end of the observation period).

Figure 2: Activity Profiles in Patients with Type 1 Diabetes in a 24-hour Glucose Clamp Study

View Enlarged Table

For doses in the interval of 0.2 to 0.4 Units/kg, insulin detemir exerts more than 50% of its maximum effect from 3 to 4 hours up to approximately 14 hours after dose administration.

Figure 3 shows glucose infusion rate results from a 16-hour glucose clamp study in patients with type 2 diabetes. The clamp study was terminated at 16 hours according to protocol.

Figure 3: Activity Profiles in Patients with Type 2 Diabetes in a 16-hour Glucose Clamp Study

View Enlarged Table

Pharmacokinetics

Absorption and Bioavailability

After subcutaneous injection of LEVEMIR in healthy subjects and in patients with diabetes, insulin detemir serum concentrations had a relatively constant concentration/time profile over 24 hours with the maximum serum concentration (Cmax) reached between 6-8 hours post-dose. Insulin detemir was more slowly absorbed after subcutaneous administration to the thigh where AUC0-5h was 30-40% lower and AUC0-inf was 10% lower than the corresponding AUCs with subcutaneous injections to the deltoid and abdominal regions.

The absolute bioavailability of insulin detemir is approximately 60%.

Distribution and Elimination

More than 98% of insulin detemir in the bloodstream is bound to albumin. The results of in vitro and in vivo protein binding studies demonstrate that there is no clinically relevant interaction between insulin detemir and fatty acids or other protein-bound drugs.

Insulin detemir has an apparent volume of distribution of approximately 0.1 L/kg. After subcutaneous administration in patients with type 1 diabetes, insulin detemir has a terminal half-life of 5 to 7 hours depending on dose.

Specific Populations

Children and Adolescents- The pharmacokinetic properties of LEVEMIR were investigated in children (6-12 years), adolescents (13-17 years), and adults with type 1 diabetes. In children, the insulin detemir plasma area under the curve (AUC) and Cmax were increased by 10% and 24%, respectively, as compared to adults. There was no difference in pharmacokinetics between adolescents and adults.

Geriatrics- In a clinical trial investigating differences in pharmacokinetics of a single subcutaneous dose of LEVEMIR in young (20 to 35 years) versus elderly ( ≥ 68 years) healthy subjects, the insulin detemir AUC was up to 35% higher among the elderly subjects due to reduced clearance. As with other insulin preparations, LEVEMIR should always be titrated according to individual requirements.

Gender- No clinically relevant differences in pharmacokinetic parameters of LEVEMIR are observed between males and females.

Race- In two clinical pharmacology studies conducted in healthy Japanese and Caucasian subjects, there were no clinically relevant differences seen in pharmacokinetic parameters. The pharmacokinetics and pharmacodynamics of LEVEMIR were investigated in a clamp study comparing patients with type 2 diabetes of Caucasian, African-American, and Latino origin. Dose-response relationships for LEVEMIR were comparable in these three populations.

Renal impairment- A single subcutaneous dose of 0.2 Units/kg (1.2 nmol/kg) of LEVEMIR was administered to healthy subjects and those with varying degrees of renal impairment (mild, moderate, severe, and hemodialysis-dependent). In this study, there were no differences in the pharmacokinetics of LEVEMIR between healthy subjects and those with renal impairment. However, some studies with human insulin have shown increased circulating levels of insulin in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with renal impairment [see WARNINGS AND PRECAUTIONS].

Hepatic impairment- A single subcutaneous dose of 0.2 Units/kg (1.2 nmol/kg) of LEVEMIR was administered to healthy subjects and those with varying degrees of hepatic impairment (mild, moderate and severe). LEVEMIR exposure as estimated by AUC decreased with increasing degrees of hepatic impairment with a corresponding increase in apparent clearance. However, some studies with human insulin have shown increased circulating levels of insulin in patients with liver impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with hepatic impairment [see WARNINGS AND PRECAUTIONS].

Pregnancy- The effect of pregnancy on the pharmacokinetics and pharmacodynamics of LEVEMIR has not been studied [see Use in Specific Populations].

Smoking- The effect of smoking on the pharmacokinetics and pharmacodynamics of LEVEMIR has not been studied.

Liraglutide -No pharmacokinetic interaction was observed between liraglutide and LEVEMIR when separate subcutaneous injections of LEVEMIR 0.5 Unit/kg (single-dose) and liraglutide 1.8 mg (steady state) were administered in patients with type 2 diabetes.

Clinical Studies

The efficacy and safety of LEVEMIR given once-daily at bedtime or twice-daily (before breakfast and at bedtime, before breakfast and with the evening meal, or at 12-hour intervals) was compared to that of once-daily or twice-daily NPH insulin in open-label, randomized, parallel studies of 1155 adults with type 1 diabetes mellitus, 347 pediatric patients with type 1 diabetes mellitus, and 869 adults with type 2 diabetes mellitus. The efficacy and safety of LEVEMIR given twice-daily was compared to once-daily insulin glargine in an open-label, randomized, parallel study of 320 patients with type 1 diabetes. The evening LEVEMIR dose was titrated in all trials according to pre-defined targets for fasting blood glucose. The pre-dinner blood glucose was used to titrate the morning LEVEMIR dose in those trials that also administered LEVEMIR in the morning. In general, the reduction in glycosylated hemoglobin (HbA1c) with LEVEMIR was similar to that with NPH insulin or insulin glargine.

Type 1 Diabetes – Adult

In a 16-week open-label clinical study (Study A, n=409), adults with type 1 diabetes were randomized to treatment with either LEVEMIR at 12-hour intervals, LEVEMIR administered in the morning and bedtime or NPH insulin administered in the morning and bedtime. Insulin aspart was also administered before each meal. At 16 weeks of treatment, the combined LEVEMIR-treated patients had similar HbA1c and fasting plasma glucose (FPG) reductions compared to the NPH-treated patients (Table 9). Differences in timing of LEVEMIR administration had no effect on HbA1c, fasting plasma glucose (FPG), or body weight.

In a 26-week, open-label clinical study (Study B, n=320), adults with type 1 diabetes were randomized to twice-daily LEVEMIR (administered in the morning and bedtime) or once-daily insulin glargine (administered at bedtime). Insulin aspart was administered before each meal. LEVEMIR-treated patients had a decrease in HbA1c similar to that of insulin glargine-treated patients.

In a 24-week, open-label clinical study (Study C, n=749), adults with type 1 diabetes were randomized to once-daily LEVEMIR or once-daily NPH insulin, both administered at bedtime and in combination with regular human insulin before each meal. LEVEMIR and NPH insulin had a similar effect on HbA1c.

Table 9: Type 1 Diabetes Mellitus – Adult

View Enlarged Table
Type 1 Diabetes – Pediatric

Two open-label, randomized, controlled clinical studies have been conducted in pediatric patients with type 1 diabetes. One study was 26 weeks in duration and enrolled patients 6-17 years of age. The other study was 52 weeks in duration and enrolled patients 2-16 years of age. In both studies, LEVEMIR and NPH insulin were administered once- or twice-daily. Bolus insulin aspart was administered before each meal. In the 26-week study, LEVEMIR-treated patients had a mean decrease in HbA1c similar to that of NPH insulin (Table 10). In the 52-week study, the randomization was stratified by age (2-5 years, n=82, and 6-16 years, n=265) and the mean HbA1c increased in both treatment arms, with similar findings in the 2-5 year-old age group (n=80) and the 6-16 year-old age group (n=258) (Table 10).

Table 10: Type 1 Diabetes Mellitus – Pediatric

Treatment duration Treatment in combination with Study D 26 weeks NovoLog® (insulin aspart) Study I 52 weeks NovoLog® (insulin aspart)
Once- or Twice Daily LEVEMIR Once- or Twice Daily NPH Once- or Twice Daily LEVEMIR Once- or Twice Daily NPH
Number of subjects treated 232 115 177 170
HbA1c (%)
  Baseline HbA1c 8.8 8.8 8.4 8.4
Adj. mean change from baseline -0.7* -0.8* 0.3** 0.2*
  LEVEMIR - NPH 0.1 0.1
  95% CI for Treatment difference -0.1; 0.3 -0.1; 0.4
Basal insulin dose (units/day)
  Baseline mean 24 26 17 17
  Mean change from baseline 8 6 8 7
Total insulin dose (units/day)
  Baseline mean 48 50 35 34
  Mean change from baseline 9 7 10 8
Fasting blood glucose (mg/dL)
  Baseline mean 181 181 135 141
  Adj. mean change from baseline -39 -21 -10** 0**
Body weight (kg)
  Baseline mean 46.3 46.2 37.4 36.5
  Adj .Mean change from baseline 1.6* 2.7* 2 7** 3.6**
*From an ANCOVA model adjusted for baseline value, geographical region, gender and age (covariate).
**From an ANCOVA model adjusted for baseline value, country, pubertal status at baseline and age (stratification factor).
Type 2 Diabetes – Adult

In a 24-week, open-label, randomized, clinical study (Study E, n=476), LEVEMIR administered twicedaily (before breakfast and evening) was compared to NPH insulin administered twice-daily (before breakfast and evening) as part of a regimen of stable combination therapy with one or two of the following oral antidiabetic medications: metformin, an insulin secretagogue, or an alpha–glucosidase inhibitor. All patients were insulin-naïve at the time of randomization. LEVEMIR and NPH insulin similarly lowered HbA1c from baseline (Table 11).

In a 22-week, open-label, randomized, clinical study (Study F, n=395) in adults with type 2 diabetes, LEVEMIR and NPH insulin were given once- or twice-daily as part of a basal-bolus regimen with insulin aspart. As measured by HbA1c or FPG, LEVEMIR had efficacy similar to that of NPH insulin.

Table 11: Type 2 Diabetes Mellitus – Adult

Treatment duration Treatment in combination with Study E 24 weeks oral agents Study F 22 weeks insulin aspart
Twice-daily LEVEMIR Twicedaily NPH Once- or Twice Daily LEVEMIR Once- or Twice Daily NPH
Number of subjects treated 237 239 195 200
HbAlc (%)
  Baseline HbA1c 8.6 8.5 8.2 8.1
  Adj. mean change from baseline -2.0* -2.1* -0.6** -0.6**
  LEVEMIR - NPH 0.1 -0.1
  95% CI for Treatment difference (-0.0,0.3) (-0.2, 0.1)
Basal insulin dose (units/day)
  Baseline mean 18 17 22 22
  Mean change from baseline 48 28 26 15
Total insulin dose1 (units/day)
  Baseline mean - - 22 22
  Mean change from baseline - - 57 42
Fasting blood glucose2 (mg/dL)
  Baseline mean 179 173 - -
  Adj. mean change from baseline -69* -74* - -
Body weight (kg)
  Baseline mean 82.5 82.3 82.0 79.6
  Adj.Mean change from baseline 1.2* 2.8* 0.5** 1.2**
1Study E – Conducted in insulin-naïve patients
2Study F - Fasting blood glucose data not collected
*From an ANCOVA model adjusted for baseline value, country and oral antidiabetic treatment category.
**From an ANCOVA model adjusted for baseline value and country.
Combination Therapy with Metformin and Liraglutide

This 26-week open-label trial enrolled 988 patients with inadequate glycemic control (HbA1c 7-10%) on metformin ( ≥ 1500 mg/day) alone or inadequate glycemic control (HbA1c 7-8.5%) on metformin ( ≥ 1500 mg/day) and a sulfonylurea. Patients who were on metformin and a sulfonylurea discontinued the sulfonylurea then all patients entered a 12-week run-in period during which they received add-on therapy with liraglutide titrated to 1.8 mg once-daily. At the end of the run-in period, 498 patients (50%) achieved HbA1c < 7% with liraglutide 1.8 mg and metformin and continued treatment in a nonrandomized, observational arm. Another 167 patients (17%) withdrew from the trial during the run-in period with approximately one-half of these patients doing so because of gastrointestinal adverse reactions [see ADVERSE REACTIONS]. The remaining 323 patients with HbA1c ≥ 7% (33% of those who entered the run-in period) were randomized to 26 weeks of once-daily LEVEMIR administered in the evening as add-on therapy (N=162) or to continued, unchanged treatment with liraglutide 1.8 mg and metformin (N=161). The starting dose of LEVEMIR was 10 units/day and the mean dose at the end of the 26-week randomized period was 39 units/day. During the 26-week randomized treatment period, the percentage of patients who discontinued due to ineffective therapy was 11.2% in the group randomized to continued treatment with liraglutide 1.8 mg and metformin and 1.2% in the group randomized to addon therapy with LEVEMIR.

Treatment with LEVEMIR as add-on to liraglutide 1.8 mg + metformin resulted in statistically significant reductions in HbA1c and FPG compared to continued, unchanged treatment with liraglutide 1.8 mg + metformin alone (Table 12). From a mean baseline body weight of 96 kg after randomization, there was a mean reduction of 0.3 kg in the patients who received LEVEMIR add-on therapy compared to a mean reduction of 1.1 kg in the patients who continued on unchanged treatment with liraglutide 1.8 mg + metformin alone.

Table 12: Results of a 26-week open-label trial of LEVEMIR as add on to liraglutide + metformin compared to continued treatment with liraglutide + metformin alone in patients not achieving HbA1c < 7% after 12 weeks of Metformin and Liraglutide

  Study H
LEVEMIR + Liraglutide +Metformin Liraglutide+ Metformin
Intent-to-Treat Population (N)a 162 157
HbA1c (%) (Mean)
  Baseline (week 0) 7.6 7.6
  Adjusted mean change from baseline -0.5* 0*
  Difference from liraglutide + metformin arm (LS mean) b 95% Confidence Interval -0.5*** (-0.7, -0.4)
Percentage of patients achieving A1c < 7% * * 4 17**
Fasting Plasma Glucose (mg/dL) (Mean)
  Baseline (week 0) 166 159
  Adjusted mean change from baseline -38* -7*
  Difference from liraglutide + metformin arm (LS mean) b -31***
  95% Confidence Interval (-39 , -23)
aIntent-to-treat population using last observation on study
bLeast squares mean adjusted for baseline value
*From an ANCOVA model adjusted for baseline value, country and previous oral antidiabetic treatment category.
**From a logistic regression model adjusted for baseline HbA1c.
***p-value < 0.0001

Pregnancy

A randomized, open-label, controlled clinical trial has been conducted in pregnant women with type 1 diabetes. [see Use in Specific Populations]

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

LEVEMIR®
(LEV–uh-mere)
(insulin detemir [rDNA origin]) Injection

What is Levemir?

  • Levemir is a man-made insulin that is used to control high blood sugar in adults and children with diabetes mellitus.
  • Levemir is not meant for use to treat diabetic ketoacidosis.

Who should not take Levemir?

Do not take Levemir if you:

  • have an allergy to Levemir or any of the ingredients in Levemir.

Before taking Levemir, tell your healthcare provider about all your medical conditions including, if you are:

  • pregnant, planning to become pregnant, or are breastfeeding.
  • taking new prescription or over-the-counter medicines, vitamins, or herbal supplements.

Before you start taking Levemir, talk to your healthcare provider about low blood sugar and how to manage it.

How should I take Levemir?

  • Read the Instructions for Use that come with your Levemir.
  • Take Levemir exactly as your healthcare provider tells you to.
  • Know the type and strength of insulin you take. Do not change the type of insulin you take unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you take different types of insulin.
  • Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.
  • Do not share your Levemir FlexPen, FlexTouch or needles with another person. You may give another person an infection or get an infection from them.
  • Never inject Levemir into a vein or muscle.

What should I avoid while taking Levemir?

While taking Levemir do not:

  • Drive or operate heavy machinery, until you know how Levemir affects you.
  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

What are the possible side effects of Levemir?

Levemir may cause serious side effects that can lead to death, including:

Low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:

  • dizziness or light-headedness
  • blurred vision
  • anxiety, irritability, or mood changes
  • sweating
  • slurred speech
  • hunger
  • confusion
  • shakiness
  • headache
  • fast heart beat

Your insulin dose may need to change because of:

  • change in level of physical activity or exercise
  • increased stress
  • change in diet
  • weight gain or loss
  • illness

Other common side effects of Levemir may include:

  • Reactions at the injection site, itching, rash, serious allergic reactions (whole body reactions), skin thickening or pits at the injection site (lipodystrophy), weight gain, and swelling of your hands and feet.

Get emergency medical help if you have:

  • trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.

These are not all the possible side effects of Levemir. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Levemir.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

You can ask your pharmacist or healthcare provider for information about Levemir that is written for health professionals. Do not use Levemir for a condition for which it was not prescribed. Do not give Levemir to other people, even if they have the same symptoms that you have. It may harm them.  

What are the ingredients in Levemir?

Active Ingredient: insulin detemir (rDNA origin)

Inactive Ingredients: zinc, m-cresol, glycerol, phenol, disodium phosphate dihydrate, sodium chloride and water for injection. Hydrochloric acid or sodium hydroxide may be added.

Instructions for Use

Levemir®
(LEV–uh-mere)
FlexTouch® Pen (insulin detemir [rDNA origin] injection)

  • Levemir FlexTouch Pen (“Pen”) is a prefilled disposable pen containing 300 units of U-100 Levemir (insulin detemir [rDNA origin] injection) insulin. You can inject from 1 to 80 units in a single injection.
  • Do not share your Levemir FlexTouch Pen with another person. You may give an infection to them or get an infection from them.
  • This Pen is not recommended for use by the blind or visually impaired without the assistance of a person trained in the proper use of the product.

Supplies you will need to give your Levemir injection:

  • Levemir FlexTouch Pen
  • a new NovoFine or NovoTwist needle
  • alcohol swab
  • 1 sharps container for throwing away used Pens and needles. See “Disposing of used Levemir FlexTouch Pens and needles” at the end of these instructions.

Preparing your Levemir FlexTouch Pen:

  • Wash your hands with soap and water.
  • Before you start to prepare your injection, check the Levemir FlexTouch Pen label to make sure you are taking the right type of insulin. This is especially important if you take more than 1 type of insulin.
  • Levemir should look clear and colorless. Do not use Levemir if it is thick, cloudy, or is colored.
  • Do not use Levemir past the expiration date printed on the label or 42 days after you start using the Pen.
  • Always use a new needle for each injection to help ensure sterility and prevent blocked needles.

Figure A

View Enlarged Table

Step 1:

  • Pull Pen cap straight off (See Figure B)

Figure B

Pull Pen cap straight off - Illustration

Step 2:

  • Check the liquid in the Pen (See Figure C). Levemir should look clear and colorless. Do not use it if it looks cloudy or colored.

Figure C

Check the liquid - Illustration

Step 3:

  • Select a new needle.
  • Pull off the paper tab from the outer needle cap (See Figure D).

Figure D

Pull off the paper tab - Illustration

Step 4:

  • Push the capped needle straight onto the Pen and twist the needle on until it is tight (See Figure E).

Figure E

Push the capped needle - Illustration

Step 5:

  • Pull off the outer needle cap. Do not throw it away (See Figure F).

Figure F

Pull off the outer needle cap - Illustration

Step 6:

  • Pull off the inner needle cap and throw it away (See Figure G).

Figure G

Pull off the inner needle cap - Illustration

Priming your Levemir FlexTouch Pen:

Step 7:

  • Turn the dose selector to select 2 units (See Figure H).

Figure H

Turn the dose selector to select 2 units - Illustration

Step 8:

  • Hold the Pen with the needle pointing up. Tap the top of the Pen gently a few times to let any air bubbles rise to the top (See Figure I).

Figure I

Tap the top of the Pen gently - Illustration

Step 9:

  • Hold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter shows “0”. The “0” must line up with the dose pointer.
  • A drop of insulin should be seen at the needle tip (See Figure J).
    • If you do not see a drop of insulin, repeat steps 7 to 9, no more than 6 times.
    • If you still do not see a drop of insulin, change the needle and repeat steps 7 to 9.

Figure J

A drop of insulin should be seen at the needle tip - Illustration

Selecting your dose:

Step 10:

  • Turn the dose selector to select the number of units you need to inject. The dose pointer should line up with your dose (See Figure K).
    • If you select the wrong dose, you can turn the dose selector forwards or backwards to the correct dose.
    • The even numbers are printed on the dial.
    • The odd numbers are shown as

Figure K

Select your dose - Illustration
  • The Levemir FlexTouch Pen insulin scale will show you how much insulin is left in your Pen (See Figure L).

Figure L

Indicator window - Illustration
  • To see how much insulin is left in your Levemir FlexTouch Pen:
    • Turn the dose selector until it stops. The dose counter will line up with the number of units of insulin that is left in your Pen. If the dose counter shows 80, there are at least 80 units left in your Pen.
    • If the dose counter shows less than 80, the number shown in the dose counter is the number of units left in your Pen.

Giving your injection:

  • Inject your Levemir exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you need to pinch the skin before injecting.
  • Levemir can be injected under the skin (subcutaneously) of your stomach area (abdomen), buttocks, upper legs (thighs) or upper arms.
  • Change (rotate) your injection sites within the area you choose for each dose. Do not use the same injection site for each injection.

Step 11:

  • Choose your injection site and wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose (See Figure M).

Figure M

Choose your injection site - Illustration

Step 12:

  • Insert the needle into your skin (See Figure N).
  • Make sure you can see the dose counter. Do not cover it with your fingers, this can stop your injection. (Figure N)

Figure N

Insert the needle into your skin - Illustration

Step 13:

  • Press and hold down the dose button until the dose counter shows “O” (See Figure O).
  • The “O” must line up with the dose pointer. You may then hear or feel a click.

Figure O

Press and hold down the dose button - Illustration
  • Keep the needle in your skin after the dose counter has returned to “0” and slowly count to 6 (See Figure P).

Figure P

Keep the needle in your skin - Illustration
  • When the dose counter returns to “O”, you will not get your full dose until 6 seconds later.
  • If the needle is removed before you count to 6, you may see a stream of insulin coming from the needle tip.
  • If you see a stream of insulin coming from the needle tip you will not get your full dose. If this happens you should check your blood sugar levels more often because you may need more insulin.

Step 14:

  • Pull the needle out of your skin (See Figure Q).
    • If you see blood after you take the needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol swab. Do not rub the area.

Figure Q

Pull the needle out - Illustration

Step 15:

  • Carefully remove the needle from the Pen and throw it away (See Figure R).

Figure R

Carefully remove the needle - Illustration
    • Do not recap the needle.
  • Recapping the needle can lead to needle stick injury. If you do not have a sharps container, carefully slip the needle into the outer needle cap (See Figure S). Safely remove the needle and throw it away as soon as you can.
    • Do not store the Pen with the needle attached. Storing without the needle attached helps prevent leaking, blocking of the needle, and air from entering the Pen.

Figure S

Slip the needle into the outer needle cap - Illustration

Step 16:

  • Replace the Pen cap by pushing it straight on (See Figure T).

Figure T

Replace the Pen cap - Illustration

After your injection:

  • Put your used Levemir FlexTouch Pen and needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic
    • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out
    • upright and stable during use
    • leak-resistant
    • properly labeled to warn of hazardous waste inside the container
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about the safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

How should I store my Levemir FlexTouch Pen?

  • Store unused Levemir FlexTouch Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
  • Store the Pen you are currently using out of the refrigerator below 86OF.
  • Do not freeze Levemir. Do not use Levemir if it has been frozen.
  • Keep Levemir away from heat or light.
  • Unused Pens may be used until the expiration date printed on the label, if kept in the refrigerator.
  • The Levemir FlexTouch Pen you are using should be thrown away after 42 days, even if it still has insulin left in it.

General Information about the safe and effective use of Levemir.

  • Keep Levemir FlexTouch Pens and needles out of the reach of children.
  • Always use a new needle for each injection.
  • Do not share Pens or needles.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

INSULIN DETEMIR - INJECTION

 

(IN-su-lin DET-e-mir)

 

COMMON BRAND NAME(S): Levemir

 

USES: Insulin detemir is used with a proper diet and exercise program to control high blood sugar in people with diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

Insulin detemir is a man-made product that is similar to human insulin. It replaces the insulin that your body would normally make. It acts longer than regular insulin, providing a low, steady level of insulin. It works by helping blood sugar (glucose) get into cells so your body can use it for energy. Insulin detemir may be used with a shorter-acting insulin product. It may also be used alone or with other diabetes drugs (such as metformin, exenatide).

 

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this medication and each time you get a refill. If you have any questions, ask your doctor, diabetes educator, or pharmacist.

Learn all preparation and usage instructions from your health care professional and the product package.

Before using, check this product visually for particles or discoloration. If either is present, do not use the insulin. Insulin detemir should be clear and colorless.

Before injecting each dose, clean the injection site with rubbing alcohol. Change the injection site each time to lessen injury under the skin and to avoid developing problems under the skin (lipodystrophy). Insulin detemir may be injected in the stomach area, the thigh, or the back of the upper arm. Do not inject into a vein or muscle because very low blood sugar (hypoglycemia) may occur. Do not rub the area after the injection. Do not inject into skin that is red, swollen, or itchy. Do not inject cold insulin because this can be painful. The insulin container you are currently using can be kept at room temperature (see also Storage section). Do not shake the container.

Inject this medication under the skin as directed by your doctor, usually once or twice daily. Insulin detemir is usually injected with the evening meal or at bedtime. If you are using it twice a day, inject as directed by your doctor, usually your first dose in the morning and your second dose with the evening meal, at bedtime, or 12 hours after the morning dose.

This product should not be mixed with any other insulin. Do not use insulin detemir in an infusion pump.

Do not change brands or types of insulin without directions on how to do so from your doctor.

Learn how to store and discard medical supplies safely.

The dosage is based on your medical condition and response to treatment. Measure each dose very carefully because even small changes in the amount of insulin may have a large effect on your blood sugar levels.

Check your urine/blood sugar level as directed by your doctor. Keep track of your results and share them with your doctor. This is very important in order to determine the correct insulin dose.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.

Consumer Overview Side Effect

SIDE EFFECTS: Injection site reactions (such as pain, redness, irritation) and swelling of the hands/feet may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: signs of low potassium level in the blood (such as muscle cramps, weakness, irregular heartbeat).

This medication can cause low blood sugar (hypoglycemia). This may occur if you do not consume enough calories from food or if you do unusually heavy exercise. Symptoms of low blood sugar include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you don't have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda. Tell your doctor immediately about the reaction and the use of this product. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Check with your doctor or pharmacist to find out what you should do if you miss a meal.

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor immediately. Your dosage may need to be increased.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Levemir (insulin detemir) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using insulin detemir, tell your doctor or pharmacist if you are allergic to it; or to other types of insulins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Do not use this medication when you have low blood sugar (hypoglycemia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: adrenal/pituitary gland problems, kidney disease, liver disease, thyroid problems.

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely.

Limit alcohol while taking this medication because it can increase the risk of developing low blood sugar.

It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Check your blood sugar readings before and after exercise. You may need a snack before exercising.

If traveling across time zones, ask your doctor about how to adjust your insulin schedule. Take extra insulin and supplies with you.

Older adults may be more sensitive to the side effects of this drug, especially low blood sugar.

Children may be more sensitive to the side effects of this drug, especially low blood sugar.

Tell your doctor right away if you are pregnant. Pregnancy may cause or worsen diabetes. Discuss a plan with your doctor for managing your blood sugar while pregnant. Your doctor may change your diabetes treatment during your pregnancy (such as diet and medications including insulin).

This medication passes into breast milk, but is unlikely to harm a nursing infant. Consult your doctor before breast-feeding. Your insulin needs may change while breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

A product that may interact with this drug is: rosiglitazone.

Beta-blocker medications (such as metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of low blood sugar, such as dizziness, hunger, or sweating, are unaffected by these drugs.

Many drugs can affect your blood sugar levels, making it more difficult to control your blood sugar. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor about the results and of any symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your anti-diabetic medication, exercise program, or diet.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: signs of low blood sugar such as sweating, shakiness, loss of consciousness, fast heartbeat.

 

NOTES: Do not share this medication, needles, or syringes with others.

Attend a diabetes education program to learn more about diabetes and the important aspects of its treatment, including medications, diet, exercise, and getting regular eye/foot/medical exams.

Learn the symptoms of high and low blood sugar and how to treat low blood sugar. Check your blood sugar levels regularly as directed.

Keep all regular medical and laboratory appointments. Laboratory and/or medical tests (such as liver and kidney function tests, fasting blood glucose, hemoglobin A1c, complete blood counts) should be performed periodically to monitor your progress or check for side effects.

Keep extra supplies of insulin, syringes, and needles on hand.

 

MISSED DOSE: It is very important to follow your insulin regimen exactly. Ask your doctor ahead of time what you should do if you miss a dose of insulin.

 

STORAGE: It is best to refrigerate all unopened insulin products. Unopened insulin detemir may also be stored at room temperature, but it must be thrown away after 42 days. Opened insulin detemir vials may be stored in the refrigerator or at room temperature. Opened insulin detemir cartridges and pens can only be stored at room temperature and should not be refrigerated. Throw away all insulin detemir in use after 42 days, even if there is insulin left. Also throw away all insulin products after the expiration date on the package. Do not freeze and do not use insulin that has been frozen.

Protect insulin from light and heat. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised March 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Levemir, Levemir FlexPen

Generic Name: insulin detemir (Pronunciation: IN su lin DE te mir)

  • What is insulin detemir (Levemir)?
  • What are the possible side effects of insulin detemir (Levemir)?
  • What is the most important information I should know about insulin detemir (Levemir)?
  • What should I discuss with my healthcare provider before using insulin detemir (Levemir)?
  • How should I use insulin detemir (Levemir)?
  • What happens if I miss a dose (Levemir)?
  • What happens if I overdose (Levemir)?
  • What should I avoid while using insulin detemir (Levemir)?
  • What other drugs will affect insulin detemir (Levemir)?
  • Where can I get more information?

What is insulin detemir (Levemir)?

Insulin detemir is a man-made form of insulin, a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. Insulin detemir is a long-acting form of insulin that is slightly different from other forms of insulin that are not man-made.

Insulin detemir is used to treat type 2 diabetes in adults.

Insulin detemir is also used to treat type 1 diabetes in adults and children who are at least 2 years old.

Insulin detemir may also be used for purposes not listed in this medication guide.

What are the possible side effects of insulin detemir (Levemir)?

Get emergency medical help if you have any of these signs of insulin allergy: itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating, or feeling like you might pass out.

Call your doctor at once if you have a serious side effect such as:

  • itching, swelling, or redness where you inject insulin detemir;
  • swelling in your hands or feet; or
  • low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Less serious side effects may include:

  • thickening of the skin where you inject insulin detemir;
  • weight gain;
  • mild headache, back pain;
  • stomach pain; or
  • flu symptoms, or cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Levemir (insulin detemir) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about insulin detemir (Levemir)?

You should not use this medication if you are allergic to insulin detemir, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with a short-acting insulin).

Many other drugs can potentially interfere with the effects of insulin detemir. It is extremely important that you tell your doctor about all the prescription and over-the-counter medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. An insulin overdose can cause life-threatening hypoglycemia. Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating. Be sure your family and close friends know how to help you in an emergency.

Side Effects Centers
  • Levemir

Patient Detailed How Take

What should I discuss with my healthcare provider before using insulin detemir (Levemir)?

You should not use this medication if you are allergic to insulin detemir, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with a short-acting insulin).

To make sure you can safely take insulin detemir, tell your doctor if you have liver or kidney disease, or if you are taking any other medications.

FDA pregnancy category B. Insulin detemir is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether insulin detemir passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use insulin detemir (Levemir)?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office. Visit your doctor regularly.

Insulin detemir is injected under the skin. You may be shown how to use injections at home. Do not self inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes. If you use this medicine once daily, use the injection at your evening meal or at bedtime. If you use the medicine twice daily, use your evening dose at least 12 hours after your morning dose.

Your doctor may want you to use a short-acting insulin in addition to insulin detemir. Always inject your insulins separately. Do not mix or dilute insulin detemir with any other insulin. Do not use an insulin pump.

Insulin detemir should be thin, clear, and colorless. Do not use the medicine if it looks cloudy, has changed colors, or has any particles in it. Call your doctor for a new prescription. Choose a different place in your injection skin area each time you use this medication. Do not inject into the same place two times in a row.

Never share an injection pen or cartridge with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another.

Needles may not be included with the injection pen. Ask your doctor or pharmacist which brand and type of needle to use with the pen. Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating.

Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection. Be sure your family and close friends know how to help you in an emergency.

Also watch for signs of blood sugar that is too high (hyperglycemia). These symptoms include increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.

Your doctor may want you to stop taking insulin detemir for a short time if you become ill, have a fever or infection, or if you have surgery or a medical emergency.

Ask your doctor how to adjust your insulin detemir dose if needed. Do not change your medication dose or schedule without your doctor's advice.

Storing unopened vials or injection pens: Keep in the carton and store in a refrigerator, protected from light. Throw away any insulin not used before the expiration date on the medicine label.

Unopened vials or injection pens may also be stored at room temperature for up to 42 days, away from heat and bright light.

Storing vials after your first use: Keep the "in-use" vials in a refrigerator or at room temperature.

Storing injection pens after your first use: Keep the "in-use" injection pens at room temperature. Do not refrigerate.

Throw away any insulin detemir kept at room temperature and not used within 42 days.

Do not freeze insulin detemir, and throw away the medication if it has become frozen.

Side Effects Centers
  • Levemir

Patient Detailed Avoid Taking

What happens if I miss a dose (Levemir)?

Follow your doctor's directions if you miss a dose of insulin. It is important to keep insulin detemir on hand at all times. Get your prescription refilled before you run out of medicine completely.

What happens if I overdose (Levemir)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An insulin overdose can cause life-threatening hypoglycemia.

Symptoms of severe hypoglycemia include extreme weakness, confusion, tremors, sweating, fast heart rate, trouble speaking, nausea, vomiting, rapid breathing, fainting, and seizure (convulsions).

What should I avoid while using insulin detemir (Levemir)?

Do not change the brand of insulin detemir or syringe you are using without first talking to your doctor or pharmacist.

Avoid drinking alcohol. It can lower your blood sugar.

What other drugs will affect insulin detemir (Levemir)?

Tell your doctor about all other medications you use, especially other diabetes medications such as:

  • exenatide (Byetta, Bydureon);
  • liraglutide (Victoza); or
  • any oral (taken by mouth) diabetes medications, especially metformin (Glucophage, Actoplus Met, Avandamet, Glucovance, Janumet, Jentadueto, Kombiglyze, Metaglip, or Prandimet).

Using certain medicines can make it harder for you to tell when you have low blood sugar. Tell your doctor if you use any of the following:

  • asthma medication;
  • cholesterol-lowering medication;
  • heart or blood pressure medication, including a diuretic (water pill);
  • medicine to treat depression or psychiatric disorders;
  • steroid medication;
  • sulfa drugs; or
  • thyroid replacement medication.

This list is not complete and there are many other drugs that can increase or decrease the effects of insulin detemir on lowering your blood sugar. Tell your doctor about all medications you use; prescription and over the counter drugs, vitamins, minerals, or herbal products. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about insulin detemir.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 7.02. Revision date: 6/12/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers
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